Consensus recommendations for the treatment and management of patients with Fabry disease on migalastat: a modified Delphi study

Daniel G Bichet; Robert J Hopkin; Patrício Aguiar; Sridhar R Allam; Yin-Hsiu Chien; Roberto Giugliani; Staci Kallish; Sabina Kineen; Olivier Lidove; Dau-Ming Niu; Iacopo Olivotto; Juan Politei; Paul Rakoski; Roser Torra; Camilla Tøndel; Derralynn A Hughes

doi:10.3389/fmed.2023.1220637

Consensus recommendations for the treatment and management of patients with Fabry disease on migalastat: a modified Delphi study

Front Med (Lausanne). 2023 Sep 1:10:1220637. doi: 10.3389/fmed.2023.1220637. eCollection 2023.

Authors

Daniel G Bichet¹, Robert J Hopkin², Patrício Aguiar^{3

4}, Sridhar R Allam^{5

6}, Yin-Hsiu Chien^{7

8}, Roberto Giugliani^{9

10}, Staci Kallish¹¹, Sabina Kineen¹², Olivier Lidove^{13

14}, Dau-Ming Niu^{15

16}, Iacopo Olivotto¹⁷, Juan Politei¹⁸, Paul Rakoski¹², Roser Torra¹⁹, Camilla Tøndel^{20

21}, Derralynn A Hughes²²

Affiliations

¹ Department of Medicine, Pharmacology and Physiology, Hôpital du Sacré-Coeur, University of Montréal, Montreal, QC, Canada.
² Department of Pediatrics, Division of Human Genetics, University of Cincinnati College of Medicine, and Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States.
³ Inborn Errors of Metabolism Reference Center, Centro Hospitalar Universitário Lisboa Norte, Lisbon, Portugal.
⁴ Faculty of Medicine, Lisbon University, Lisbon, Portugal.
⁵ Burnett School of Medicine, Texas Christian University, Fort Worth, TX, United States.
⁶ Tarrant Nephrology Associates/PPG Health, Fort Worth, TX, United States.
⁷ Department of Medical Genetics, National Taiwan University Hospital, Taipei, Taiwan.
⁸ Department of Pediatrics, National Taiwan University College of Medicine, Taipei, Taiwan.
⁹ Postgraduate Program in Genetics and Molecular Biology (PPGBM) at Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, Brazil.
¹⁰ BioDiscovery Laboratory at Hospital de Clinicas de Porto Alegre (HCPA), National Institute of Population Medical Genetics (INAGEMP), DASA, Casa dos Raros, Porto Alegre, Brazil.
¹¹ Division of Translational Medicine and Human Genetics, Department of Medicine, University of Pennsylvania, Philadelphia, PA, United States.
¹² Patient Advocate, United States.
¹³ Department of Internal Medicine-Rheumatology, Croix Saint Simon Hospital, Paris, France.
¹⁴ French Network of Inherited Metabolic Disorders (G2m), France.
¹⁵ Department of Pediatrics, Taipei Veterans General Hospital, Taipei, Taiwan.
¹⁶ Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
¹⁷ Department of Experimental and Clinical Medicine, Meyer University Children's Hospital, Florence, Italy.
¹⁸ Department of Neurology, Fundacion Para el Estudio de Enfermedades Neurometabolicas (FESEN), Buenos Aires, Argentina.
¹⁹ Inherited Kidney Disorders, Department of Nephrology, Fundació Puigvert, Institut d'Investigació Biomèdica Sant Pau (IIB-SANT PAU), Universitat Autònoma de Barcelona, Barcelona, Spain.
²⁰ Department of Clinical Science, University of Bergen, Bergen, Norway.
²¹ Department of Pediatrics, Haukeland University Hospital, Bergen, Norway.
²² Lysosomal Storage Disorders Unit, Royal Free London NHS Foundation Trust and University College London, London, United Kingdom.

Abstract

Objective: Fabry disease is a progressive disorder caused by deficiency of the α-galactosidase A enzyme (α-Gal A), leading to multisystemic organ damage with heterogenous clinical presentation. The addition of the oral chaperone therapy migalastat to the available treatment options for Fabry disease is not yet universally reflected in all treatment guidelines. These consensus recommendations are intended to provide guidance for the treatment and monitoring of patients with Fabry disease receiving migalastat.

Methods: A modified Delphi process was conducted to determine consensus on treatment decisions and monitoring of patients with Fabry disease receiving migalastat. The multidisciplinary panel comprised 14 expert physicians across nine specialties and two patients with Fabry disease. Two rounds of Delphi surveys were completed and recommendations on the use of biomarkers, multidisciplinary monitoring, and treatment decisions were generated based on statements that reached consensus.

Results: The expert panel reached consensus agreement on 49 of 54 statements, including 16 that reached consensus in round 1. Statements that reached consensus agreement are summarized in recommendations for migalastat treatment and monitoring, including baseline and follow-up assessments and frequency. All patients with Fabry disease and an amenable mutation may initiate migalastat treatment if they have evidence of Fabry-related symptoms and/or organ involvement. Treatment decisions should include holistic assessment of the patient, considering clinical symptoms and organ involvement as well as patient-reported outcomes and patient preference. The reliability of α-Gal A and globotriaosylsphingosine as pharmacodynamic response biomarkers remains unclear.

Conclusion: These recommendations build on previously published guidelines to highlight the importance of holistic, multidisciplinary monitoring for patients with Fabry disease receiving migalastat, in addition to shared decision-making regarding treatments and monitoring throughout the patient journey. GRAPHICAL ABSTRACT.

Keywords: alpha-galactosidase A; amenability; chaperone therapy; globotriaosylsphingosine; patient journey; treatment decisions.